This clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cancer cells before, and may prevent the myelodysplastic syndrome from coming back after the transplant. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Patients in which adequate marrow/biopsy specimens cannot be obtained to determine disease burden by morphologic assessment, but have fulfilled criteria (abnormal myeloblast count >= 5% and < 20%) by flow cytometry are still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures

Patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion; the attending may use metrics such as Treatment Related Mortality Score (TRM) or Karnofsky performance status, in addition to clinical values (age, platelet count, serum albumin, secondary or de novo disease, white blood cell count, peripheral blood blast percentage, and serum creatinine) to determine if a patient should be included

Considered a potential transplant candidate; the attending physician will determine transplant candidacy at the time of initial visit

Human leukocyte antigen (HLA)-typing must be requested by the time of enrollment, but does not need to be resulted to enroll

Males should be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Women must be postmenopausal or must be willing to use an acceptable method of contraception to avoid pregnancy for the entire period of the study and for at least 3 months after the study; a postmenopausal woman is defined as a woman who has experienced amenorrhea > 12 consecutive months or a woman on hormone replacement therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for patients in whom menopausal state is in question, a negative pregnancy test will be required prior to enrollment

Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Exclusions (conditions that would prevent participation in this study)

A diagnosis of acute promyelocytic leukemia as defined by the 2008 World Health Organization classification system

Use of any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea

Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment

Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)

Pregnant or lactating patients

Any uncontrolled or significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results

Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)